Identification of cofilin-1 as a novel mediator for the metastatic potentials and chemoresistance of the prostate cancer cells

Abstract

Prostate cancer (PCa) is the most common malignancy among men. Tumor metastasis and chemoresistance contribute to the major cause of the mortality. In this study, we compared the protein profiles of two prostate cancer cell lines with different metastatic potentials, and identified cofilin-1 (CFL1) was one of the most differentially expressed proteins between two cell lines. Further results suggested that cofilin-1 promoted the remodeling of F-actin cytoskeleton, and enhanced the proliferation, migration and invasion of the prostate cancer cells via activation of P38 MAPK signaling pathway. In addition, cofilin-1 elevated the expression and drug efflux activity of multidrug resistance protein 1 (MDR1) by P38 MAPK signaling pathway, resulting in decrease of the adriamycin-induced apoptosis as well as the lytic cell death, and the subsequent resistance against adriamycin. Collectively, cofilin-1 might serve as a novel target candidate for both inhibiting the metastasis and reversing the chemoresistance of PCa.